Cocaine dependence has long been thought of as a psychological addiction without a physiological withdrawal syndrome. In animals, chronic cocaine administration produces multiple neurophysiological adaptations that may decrease activity in brain reward pathways. Recent clinical research suggests that cocaine abstinence symptoms include anhedonia, which is consistent with the decreased reward in preclinical studies. Thus, severe cocaine abuse appears to produce a neurophysiological addiction having a primarily psychological clinical expression. Recent research has produced encouraging preliminary data on general pharmacological therapies for cocaine abuse and on specific agents for treating cocaine abusers who have coexisting axis I psychiatric disorders.